Immunity system complexity: role of Vitamin D and gut biome (Introduction)

by David Turell , Sunday, July 21, 2024, 18:59 (125 days ago) @ David Turell

A study in mice:

https://www.the-scientist.com/vitamin-d-acts-via-the-microbiome-to-boost-cancer-immunit...

"They found that vitamin D acts through a binding protein, Gc globulin, and the gut resident Bacteroides fragilis to stimulate antitumor immunity in mice. These findings demonstrate for the first time a connection between vitamin D metabolism, a specific species of the microbiome, and the immune response to cancer in a living organism.

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"Vitamin D is best known for its role in bone growth and development, where it facilitates the absorption of calcium, phosphate, and magnesium. More than a century ago, deficiency of this vitamin was identified as the cause of the bone disease rickets. Since then, researchers have found vitamin D to potentially play in a role in a number of other conditions, including cardiovascular diseases, autoimmunity, and cancer. However, vitamin D does not act alone. Recent evidence suggests that the gut microbiome, located at the interface of the intestinal lumen and epithelia where dietary vitamin D is absorbed, works synergistically with this vitamin to modulate the immune system. (my bold)

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"When Reis e Sousa and his team investigated the secreted form of the actin-severing protein gelsolin (sGSN), which is produced by damaged and cancerous cells, they found that lower levels of sGSN expression, or mutations in actin-associated proteins, correlated with enhanced antitumor immunity and increased patient survival.

“'The serendipity comes from the fact that Gc globulin has a separate actin-binding domain and functions as an actin scavenger with secreted gelsolin,” he noted.

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"The fecal transplant experiment confirmed that the tumor resistance was transmissible. The team also observed that treating the Gc-deficient mice with antibiotics diminished their tumor resistance following fecal transplant, further implicating the gut microbiome. They found that this resistance was enhanced when they fed the mice a high-vitamin D diet. The fact that they did not observe this effect in mice with deficiencies in other immunity-related genes that underwent the same treatments validated Gc as the protein linking vitamin D metabolism with the gut microbiome.

"Next, Reis e Sousa and his colleagues zeroed in on which microbiome species might confer this resistance. Shotgun metagenomic analysis revealed that one species, B. fragilis, was marginally elevated in the fecal samples from mice on a high vitamin D diet. When the team administered B. fragilis to the mice orally, they noted tumor immunity in mice on a standard vitamin D diet, but not in those on a vitamin D deficient diet. “[B. fragilis] is a candidate as it can phenocopy the effects. But it might work with other microbes, and we need to repeat the experiment in germ-free mice to assess whether other species are involved,” said Reis e Sousa.

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“'The novelty of this study is not so much that vitamin D regulates the immune response or has a role in cancer. It has not yet been reported mechanistically how vitamin D does this,” said Alessio Fasano, a gastroenterologist and nutritionist at Harvard Medical School, who was not involved in this study. “This article shows how this happens by using both animal models and a human study, and that is why it is so significant.”

"Fasano noted, "It still needs to be captured by clinical trials, but there is applicability of their findings in that vitamin D could be included in cancer treatment and vitamin D levels reported over time…There is new respect for vitamin D.'”

Comment: it has always been acknowledged that Vitamin D helped immunity. But this entangled system involving gut biome is a big surprise, and a major discovery.